Structural Screening of Short Peptide Amphiphiles with Autocatalytic Self‐Replication

Two reactive precursors generate peptide amphiphile products that can self-assemble into micelles. These micelles can catalyse precursor reactivity, triggering autocatalytic self-replication, whereby the product of the reaction catalyses the formation of molecular copies of itself. We have identified a minimal tripeptide amphiphile capable of displaying this biomimetic self-replicative behaviour.

Abstract

There is great interest in developing small synthetic molecules that imitate some of the functions and behaviour of living beings. Here, we describe the structural screening of peptide amphiphiles with autocatalytic self-replication, which mimics the perpetuation mechanisms of living matter. Our design uses two reactive precursors to generate self-assembling peptide amphiphiles, which form micelles that catalyse their own synthesis. A collection of precursors with varying sizes was screened combinatorially, revealing a minimal tripeptide amphiphile required to trigger autocatalytic self-replication. These results contribute to the structural simplification of synthetic supramolecular monomers with life-like behaviour.

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